Sreejesh Sreedharanunni

Frequency of Paroxysmal Nocturnal Hemoglobinuria Clones by Multiparametric Flow Cytometry in Pediatric Aplastic Anemia Patients of Indian Ethnic Origin

The literature on paroxysmal nocturnal hemoglobinuria (PNH) in aplastic anemia (AA) is largely focused on adults with few studies in children. Moreover, large studies are conspicuously absent from developing countries. Knowledge of the prevalence and utility of their detection is required before widespread use of PNH screening in pediatric AA in resource‐limited settings.

An analysis of transplant glomerulopathy and thrombotic microangiopathy in kidney transplant biopsies

Glomerular diseases of the transplanted kidney are the most important cause of poor long‐ term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims (i) to determine the incidence of transplant glomerulopathy (TG) and thrombotic microangiopathy (TMA) in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the histological and ultrastructural features of TG and TMA, and (iii) to assess the relationship between the two glomerular lesions. Of a total of 1792 indication renal transplant biopsies received over 5 years (2006–2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy (EM), and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody‐mediated rejection (AMR) is associated with both TG and TMA in 71% and 46.5%, respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with subendothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smoldering TMA of various causes.

Thrombotic Primary Antiphospholipid Syndrome: the profile of antibody positivity in patients from North India

We evaluated the frequency of antiphospholipid antibody syndrome (APS) in patients presenting with thrombosis of various vascular beds from North India and report the antibody profiles encountered.

Lupus anticoagulant - hypoprothrombinemia syndrome: a rare cause of intracranial bleeding.

: We report a 14-year-old girl who presented with subdural hematoma and a deranged coagulation profile suggestive of an inhibitor. Investigations revealed prothrombin deficiency along with positivity for antiphospholipid antibodies, which improved with steroid therapy. Bleeding diathesis in children and adolescents commonly results from thrombocytopenia, platelet function disorders, or coagulation factor deficiency; whereas bleeding because of coagulation factor inhibitors are extremely rare in this age group. This case also highlights the uncommon presentation of antiphospholipid antibody syndrome, as they often present with thrombosis or pregnancy complications rather than bleeding.

β-Thalassemia Intermedia Caused by Compound Heterozygosity for Hb Lepore-Hollandia and β-Thalassemia is Rare in the Indian Population

Abstract Compound heterozygosity for one of the Hb Lepore mutations and β-thalassemia (β-thal) is a rare cause of non transfusion-dependent thalassemia. We report a 4-year-old boy who presented clinically as homozygous/compound heterozygous β-thal intermedia (β-TI), an impression that was corroborated by the initial hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/β-thal was revealed after parental studies and molecular analyses including β-globin gene sequencing. Our patient highlights the importance of a logical stepwise multi modality approach and the vital importance of parental screening and molecular studies in accurate characterization of complex hemoglobinopathies. Correct diagnosis is especially crucial if pre natal detection is anticipated for future pregnancies. Molecular analyses alone may not compensate for the unavailability of parental testing. This is because the molecular results may be misinterpreted, especially if limited tests are conducted. The infrequent prior reports of this combination from distant parts of the Indian subcontinent suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in isolated families.

Spectrum of diseases diagnosed on bone marrow examination of 285 infants in a single tertiary care center

Abstract Objectives Bone marrow (BM) aspiration and trephine biopsy is one of the most valuable procedures in the evaluation of hematological disorders. There is a shortage of published literature regarding the indications, procedure, and outcome of bone marrow examination (BME) in neonates and infants. The aim of the present study is to analyze the common indications of performing BME and to assess the spectrum of disorders diagnosed from BM of neonates and infants. Methods A retrospective analysis of BMEs performed in infants over a period of 5 years, between 2009 and 2013 was done. Results and discussion A total of 297 BME were performed on 285 infants, which constitutes 10.3% of pediatric BME procedures during the same period. In our institute, BME is routinely performed by trained pathologists from posterior superior iliac spine in children including infants and neonates with an overall sample adequacy of 97%. Evaluation of cytopenias and suspicion of storage disorder were the most common indications for BME procedure, while acute leukemias and storage disorders were the most common diagnoses offered in infant BM. Conclusions Posterior superior iliac spine is a good site of BME in neonates and infants. BM trephine biopsy is a difficult procedure in this age group, however remains indispensable in situations where an infiltrative pathology is suspected. BME not only helps to make specific diagnoses but should also be used as an extremely valuable, quick, and economically viable procedure to exclude major hematological disorders including certain forms of storage disorder and hematological malignancy in this age group.

Visceral Leishmaniasis: Kala-azar.

A 30-year-old male from rural northwest India presented to our hospital with fever of 4 weeks duration associated with abdominal pain. He was a farmer by occupation and gave history of sleeping in the open. General physical examination showed pallor and subcentimetric cervical lymphadenopathy. Abdominal examination revealed massive splenomegaly (14 cm below left costal margin). Liver was palpable 4 cm below right costal margin with a span of 15 cm. Investigations revealed pancytopenia, with hemoglobin of 6.2 g/dl (13.3–16.2 g/dl), total leukocyte count of 3500/cu mm (4000–11 000 cells/µl) and platelet count of 68 000/µlitre (150 000–400 000 platelets/µl). Polyclonal hypergammaglobinemia was noted with globulin fraction—5.3 g/dl (2.0–3.5 g/dl). Liver function tests and renal function tests were normal. …

CD103+ γδ T cell large granular lymphocytosis in a patient with refractory celiac disease: a diagnostic enigma

Indolent γδ T cell lymphomas/leukemias are rare and overlap with the morphological spectrum of large granular lymphocyte (LGL) leukemia. We report an extremely rare case of CD103+ γδ T LGL leukemia in a patient with celiac disease who presented with refractory diarrhea. Whether the refractory diarrhea in our patient was a manifestation of LGL leukemia itself or whether the clonal LGL expansion is a manifestation of refractory celiac disease (RCD) remains an enigma. This report highlights the diagnostic difficulties and the need of consensus in categorizing clonal CD103+ lymphocytosis in patients with RCD.

Myeloperoxidase Deficient Acute Promyelocytic Leukemia: Report of Two Cases

Acute promyelocytic leukemia (APL) is characterized by the presence of ‘abnormal promyelocytes’ which show variable morphology but a characteristic strong myeloperoxidase (MPO) positivity on cytochemistry and immunohistochemistry (IHC). The characteristic morphology and cytochemistry is often considered as a strong evidence to make a morphological diagnosis of APL and often enough to prompt a haematologist to start all-trans-retinoic acid (ATRA), before a confirmatory molecular diagnosis arrives. We herein describe two cases of classical APL having an absent/reduced MPO activity.

Diffuse Large B Cell Lymphoma with Pseudoacinar Arrangement: A Potential Diagnostic Pitfall

A 62-year male presented with fever, weight loss and shortness of breath of 2 months duration. He had pallor, hepatosplenomegaly; anemia and thrombocytopenia. Bone marrow smears showed clusters of large pleomorphic atypical cells with frequent acinar arrangement and abundant vacuolated cytoplasm (Fig. 1a–d). No lymphoglandular (LG) bodies were seen, raising the suspicion of metastatic carcinoma. Biopsy showed sheets and interstitial excess of atypical cells with interspersed normal hematopoietic elements (Fig. 2a, b). Immunohistochemistry for Pan cytokeratin was negative, ruling out a carcinoma. Strong membranous positivity for CD45 and CD20 (Fig. 2c–e) was seen, while CD3, CD5, CD23, CD10, CD30, and cyclin D1 were negative. Together with diffuse nuclear MUM-1 positivity (C 30%) and CD10 negativity (\ 30%), a diagnosis of diffuse large B cell lymphoma (DLBCL), non-germinal center B-cell subtype was offered as per Hans-algorithm [1]. Patient succumbed to heart failure. In view of the absence of lymphadenopathy and any mass lesion on examination and imaging, the patient is likely to have primary bone marrow DLBCL. Pleomorphic lymphomas especially anaplastic large cell lymphomas are known to mimic carcinoma; however, the phenomenon is distinctly rare in DLBCL [2]. The odd features in this case were pseudoacinar arrangement and lack of LG bodies. Liberal use of